pH-Responsive Drug Release from Polymer-Coated Mesoporous

J. Phys. Chem. C 2009, 113, 12753–12758

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pH-Responsive Drug Release from Polymer-Coated Mesoporous Silica Spheres Qiang Gao,†,‡ Yao Xu,*,† Dong Wu,† Yuhan Sun,† and Xiaoan Li§ State Key Laboratory of Coal ConVersion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001, P. R. China, Graduate UniVersity of the Chinese Academy of Sciences, Beijing 100049, P. R. China, and Department of Infectious Disease, General Hospital of Chengdu Military Command, Chengdu 610083, P. R. China ReceiVed: May 11, 2009; ReVised Manuscript ReceiVed: June 2, 2009

A novel method was proposed to coat poly(methacrylic acid-co-vinyl triethoxylsilane) (PMV) on mesoporous silica spheres (MSSs) to obtain a core-shell pH-responsive drug-carrier (MSS/PMV). PMV was prepared by free radical polymerization of methacrylic acid (MAA) and vinyl triethoxylsilane (VTES), in which MAA acted as the pH-sensitive monomer and VTES acted as the siloxane-containing monomer to provide an anchoring effect with the MSS surface. The micrographs of MSSs before and after coating were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It was found that the PMV shell with a thickness of 20 nm had been coated successfully on MSS particles. To confirm the pHsensitivity of the PMV shell, we investigated the pH-response difference between MSS/PMV and MSS/ PMV-H (acidified MSS/PMV) in NH4NO3/C2H5OH solution. It was found that the PMV shell of MSS/PMV was loose (“open” state) and allowed template molecules to penetrate it easily. By contrast, the PMV shell of MSS/PMV-H was compact (“closed” state) and confined template molecules effectively inside MSS pores. These results indicated that the PMV shell played the role of molecular switch that could control the transport of molecules via a pH-dependent “open-close” mechanism. In a test of in vitro drug release, MSS/PMV showed high response to the pH of a drug solution. At high pH (pH ) 7.5), ibuprofen (IBU) that loaded in MSS/PMV released rapidly and completely (within 2 h); at low pH (pH ) 4.0 or 5.0), only a small part of the IBU (15 wt %) was slowly released from the MSS/PMV, and most of the IBU was effectively confined in MSS pores. 1. Introduction Recently, mesoporous silica nanoparticles (MSNs) were suggested as useful carriers for drug delivery because of their biocompatibility, large surface area and pore volume, adjustable pore diameter, and modifiable surface properties.1-6 For this MSN-based carrier system, extensive research has been devoted to investigating the influence of material characteristics7-10 (e.g., pore size, pore geometry, and particle morphology) and organic modifications11,12 of MSNs on drug delivery rate. These previous results indicated that unique physical-chemical properties of MSNs made them promising carriers for drug delivery.1-12 But conventional MSNs (e.g., MCM-41 and SBA-15) are unintelligent materials with which drug release cannot be accomplished in a controllable manner that precisely matches the actual physiological needs at the proper time and/or proper site. To overcome this disadvantage, one strategy was to fabricate stimuli-responsivepolymer-coatedMSNs(MSN/SRP)carriers.13-20 In such a drug-carrier system, MSNs were used as drug containers, and polymer coating was employed as a stimuliresponsive switch. In principle, the system can be sensitive to physiological conditions (e.g., pH and temperature), and accordingly release the necessary amount of drug in response. To date, several research groups have taken great efforts to explore such drug carrier systems, and developed two main coating technologies, i.e., “layer-by-layer” coating15-18,21 and surface * Corresponding author. Tel: +86-351-4049859. Fax: +86-351-4041153. E-mail: [email protected]. † Institute of Coal Chemistry, Chinese Academy of Sciences. ‡ Graduate University of the Chinese Academy of Sciences. § General Hospital of Chengdu Military Command.

radical polymerization.19 The former method was based on electrostatic attraction to assemble multilayered polyelectrolytes on an MSN surface. For the latter method, functional monomers and surface-modified MSNs were used as the starting materials to synthesize MSN/SRPs via radical polymerization. It is notable that these MSN/SRP carrier systems inherited the advantages of SRP- and MSN-based carriers, and made up for the deficiency of traditional polymer-based drug carrier systems in stability. However, complicated experimental processes were generally unavoidable when employing the method of “layer-by-layer” coating or surface radical polymerization. As a result of the relatively weak interaction (electrostatic force) between polyelectrolytes and MSNs, the “layer-by-layer” coating method needed to coat a pair of polyelectrolytes (polycation/polyanion) on the MSN surface alternatively and repeatedly. For the surface radical polymerization method, functional monomers frequently self-polymerized to result in a difficult separation of MSN/SRPs from the self-polymer. So, it is still a challenge to explore efficient ways to fabricate an MSN/SRP carrier for controlled drug delivery. Herein, we proposed a novel method to synthesize a core-shell MSN/SRP (i.e., poly(methacrylic acid-co-vinyl triethoxylsilane) (PMV) on mesoporous silica spheres (MSSs), MSS/PMV). The preparation scheme is described in Figure 1. The Sto¨ber method was employed to prepare monodisperse MSSs. Methacrylic acid (MAA) and vinyl triethoxylsilane (VTES) were used to prepare the pH-sensitive polymer PMV, where MAA acted as the pH-sensitive monomer and VTES provided PMV with anchoring groups to graft this SRP on the MSS surface successfully. The anchor mechanism of PMV on

10.1021/jp9043978 CCC: $40.75  2009 American Chemical Society Published on Web 06/25/2009

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Figure 1. Schematic illustration of the synthesis strategy of MSS/PMV and its working principle as a pH-responsive drug carrier.

MSS was based on the fact that the ≡Si-OC2H5 groups of VTES could bond specifically with the ≡Si-OH groups of MSS in the Sto¨ber solution.22 Such a covalently bonded anchor of PMV on MSS is likely to solve those above-mentioned problems that arose in the two previous methods, and perhaps make it practical in the construction of MSN/SRP drug carriers. Moreover, if successfully prepared, PMV-coated MSS may be an ideal carrier for targeting drug delivery through a pHresponsive mechanism. At low pH (e.g., the stomach), the PMV coating shrinks to block the pore openings of MSS, and thus the drug release is minimal. At neutral or high pH (e.g., the intestine), the PMV coating swells and opens the pathway for drug release from MSS (see Figure 1). 2. Experimental Details 2.1. Preparation of MSSs. MSSs were synthesized by a modified Sto¨ber method. Typically, 3 g of cetyl trimethylammonium bromide (CTAB) was dissolved in 828 mL of deionized water and mixed with 1438 mL of absolute ethanol. Then, 72 mL of aqueous ammonia solution (25 wt %) was added to this clear solution and stirred for 15 min. After the addition of 10 mL of tetraethyl orthosilicate (TEOS), the resulting mixture was stirred for 2 h to form a suspension of MSS. The MSS solids

containing templates were collected by filtration, washed with deionized water/ethanol, and vacuum-dried at 70 °C. The templates inside the MSSs were removed by ion-exchange with NH4NO3/C2H5OH: 1.0 g of MSS powder was dispersed in 150 mL of ethanol containing 0.3 g of NH4NO3, and the mixture was stirred at 70 °C for 30 min. The above treatment was repeated twice. 2.2. Preparation of PMV. The pH-sensitive polymer, PMV, was synthesized by free radical polymerization of MAA and VTES. Typically, 20 mL of MAA and 4 mL of VTES were mixed with 80 mL of absolute ethanol at room temperature. After deoxygenation by bubbling with N2 for 1 h, 50 mg of azodiisobutyronitrile was added to the mixed solution with stirring. The solution was then heated to 70 °C, and the following polymerization lasted 24 h under N2 atmosphere to form a PMV solution (solution A). The PMV solid was precipitated from solution A through n-hexane extraction. In order to remove the residual monomer, the dried PMV solid was redissolved in absolute ethanol. The above extractiondissolution process was repeated three times to obtain pure PMV solid. 2.3. Preparations of MSS/PMV and MSS/PMV-H. One gram of dried PMV powder was dissolved in 100 mL of absolute

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ethanol to form solution B. Then, solution B was dropwise added into the MSS suspension, and the mixture was stirred for 24 h. The solid products were collected by filtration, washed with deionized water/ethanol, and vacuum-dried at 70 °C. The removal of templates inside MSS/PMV was similar to that of MSS. In order to determine the pH-response of the PMV shell, a reference experiment was also carried out. First, 0.5 g of MSS/ PMV powder with template was immersed in 100 mL of 2 M HCl aqueous solution. After stirring for 0.5 h, the protonated solids, MSS/PMV-H, were collected by filtration, washed with deionized water/ethanol, and vacuum-dried at 70 °C. Finally, MSS/PMV-H was ion-exchanged three times by NH4NO3/ C2H5OH. 2.4. Drug Loading. Ibuprofen (IBU) was dissolved in hexane at a concentration of 33 mg/mL. Then, 1 g of powder MSS or MSS/PMV) was dispersed in 30 mL of this solution at room temperature. After stirring for 72 h, IBU-loading MSS or MSS/ PMV was separated by centrifugation, and dried at 50 °C. 2.5. In Vitro Drug Releases. IBU-loaded MSS or MSS/ PMV powder was immersed in release fluids with different pH values (pH ) 4.0, 5.0, and 7.5) at 37 °C with stirring at a rate of 100 rpm. The release fluid (2.0 mL) was withdrawn at a give time intervals, and supplied with the same volume of fresh release fluid. The drug concentration in the fluid was measured by ultraviolet-visible (UV-vis) spectroscopy at a wavelength of 264 nm. Calculation of the corrected concentration of released IBU is based on the following equation:

Cc ) Ct +

V V

t-1

∑ Ct

(1)

0

where Cc is the corrected concentration at time t, Ct is the apparent concentration at time t, V is the volume of sample taken, and V is the total volume of release fluid. 2.6. Materials Characterizations. The powder X-ray diffraction (XRD) patterns were recorded on a Bruker diffractometer using Cu KR radiation. A N2 adsorption-desorption isotherm was obtained on a Micromeritics Tristar 3000 pore analyzer at 77 K. Transmission electronic micrographs (TEMs) of samples were observed on Hitachi H-600. High-resolution TEMs (HRTEMs) of the samples were observed on a JEM2010. Field emission scanning electronic micrographs (FE-SEM) were obtained on an LEO 1530 VP. The UV-vis absorbance spectra were measured with a Shimadzu UV-3150 spectrophotometer. Elemental analysis of samples was determined by inductively coupled plasma-atomic emission spectrometry on a TJA AtomScan16. Fourier transform infrared spectra (FTIR) of samples were measured with Nicolet Nexus 470. Gel permeation chromatographs (GPC) of samples were recorded on a Shimadzu LC-10AD. 3. Results and Discussion 3.1. Characterizations of PMV. The molecular weight of PMV was measured by gel permeation chromatography (GPC). Figure 2 showed the GPC curve of PMV. It could be found that only one peak appeared at the retention time of 15.4 min (The negative peaks beyond 20 min corresponded to elution of solvent), indicating that the PMV had a monomodal molecular weight dispersion. The weight-average molecular weight (Mw) and the number-average molecular weight (Mn) of PMV were 3458 g/mol and 3086 g/mol, respectively (see Figure 2).

Figure 2. The GPC curve of PMV.

Figure 3. The FT-IR spectra of MSS, PMV, and MSS/PMV.

Calculated from these two values, the molecular weight distribution (MWD ) Mw/Mn) equaled 1.12. Such a narrow MWD indicated the uniform distribution of the molecular weight of PMV. From the results of elemental analysis, it was found the element contents of Si and C were 2.23 wt % and 52.87 wt %, respectively. From the weight ratio of Si to C, the molar ratio of VTES monomer to MAA monomer was determined to be about 0.085, showing a chemical composition of PMV that was very close to that of poly(methacrylic acid) (PMAA). Therefore, it was hopeful that PMV have the pH-sensitivity similar to PMAA. 3.2. Coating of PMV. FT-IR spectra of PMV, MSS, and MSS/PMV were shown in Figure 3 to ascertain the PMV coating on MSS. For PMV, the adsorption peaks at 1702 and 2994 cm-1 could be attributed to the stretching vibration of CdO in -COOH group and the stretching vibration of -CH3 group, respectively.23 The adsorption peaks at 1176, 1267, and 1451 cm-1 could be attributed to the stretching vibration of Si-O-C, the symmetric distortion vibration of Si-C bond and the asymmetric distortion vibration of Si-C bond, respectively.23 These results indicated that PMV was indeed obtained by copolymerization of MAA (containing -COOH and -CH3) and VTES (containing Si-C and Si-O-C). Also, the peaks at 1702, 2994, and 1451 cm-1 could be observed in the spectrum of MSS/ PMV (see Figure 3), indicating that PMV had successfully coated on MSS external surface. It was noteworthy that the peak (at 1267 cm-1) corresponding to the symmetric distortion vibration of Si-C bond could not be clearly recognized. Considering the low magnitude of PMV in the MSS/PMV, the possibe reason accounting for this phenomena was that the intensive and broad peak of Si-O-Si (at 1092 cm-1) covered the relatively weak peak of 1267 cm-1. SEM and TEM images of MSS, MSS/PMV, and MSS/ PMV-H are presented in Figure 4-6. Obviously, MSS were exclusively made up of uniform monodisperse spherical particles with a mean size of about 660 nm and smooth external surface

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Figure 6. FE-SEM images of MSS/PMV (a,b) and MSS/PMV-H (c,d).

Figure 4. TEM images (a,b) and FE-SEM images (c,d) of MSS.

Figure 7. HRTEM images of MSS (a) and MSS/PMV (b).

Figure 8. Powder XRD patterns of MSS and MSS/PMV.

Figure 5. TEM images of MSS/PMV (a,b) and MSS/PMV-H (c,d).

(see Figure 4). In contrast, MSS/PMV had an obviously rough surface with average diameter of about 680 nm, indicating that the PMV shell with a thickness of 20 nm had been coated successfully on MSS (see Figure 5a,b and Figure 6a,b). Noticeably, the basic condition for synthesis of MSS/PMV ionized PMV shell and made particle surface very loose. Once MSS/PMV was acidified, the obtained MSS/PMV-H accordingly showed a smooth surface (see Figure 5c,d and Figure 6c,d). This phenomenon should originate from the shrinkage of the PMV shell and confirmed that the polymer shell had obvious pH-sensitivity. Figure 7 shows the HRTEM images of MSS and MSS/PMV. MSS obviously exhibited wormlike mesopores, and the pore

size was about 2.6 nm (see Figure 7a). The results were consistent with the reported conclusion.24 For MSS/PMV, the wormlike mesoporous structure was difficult to identify (see Figure 7b) because of the shadowing effect of PMV shell on the MSS core. Also in Figure 7b, a floccule-like coating layer could be found at the edge of MSS/PMV, further confirming the existence of PMV shell. Because the PMV shell shrunk quickly under intensive electron beam of HRTEM, the flocculelike coating could not present its actual thickness of 20 nm. 3.3. Mesoporous Structures of MSS and MSS/PMV. The mesopore orderliness of the samples was investigated by XRD and N2 adsorption-desorption. XRD patterns of samples are shown in Figure 8. An obvious peak (100) could be observed for both MSS and MSS/PMV, indicating ordered mesoporous structures of MCM-41 material. Simultaneously, the (100) diffraction was less resolved after coating PMV on MSS, showing that the mesopore orderliness decreased. N2 adsorption-desorption isotherms of samples are shown in Figure 9. Both samples possessed typical type IV isotherms that are the

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Figure 9. Nitrogen adsorption-desorption isotherms and pore diameter distributions (Barrett-Joyner-Halenda (BJH)) of MSS (a) and MSS/ PMV (b) (The templates inside both samples were removed).

TABLE 1: Textural Parameters and Drug-Loaded Amounts of Samples sample

SBET (m2/g)

Vp (cm3/g)

MSSa MSSb MSS/PMVa MSS/PMVb MSS/PMV-Ha MSS/PMV-Hb

42 710 488 1050 166 203

0.046 0.396 0.319 0.633 0.186 0.193

a

IBU loading (wt %) 17.4 20.3

As-synthesized samples. b Ion-exchanged samples.

characteristics of a mesoporous solid. Also in Figure 9, it could be found that MSS and MSS/PMV had nearly equal pore sizes (about 2.6 nm), indicating that PMV coated only on the external surface of the MSS particles and the polymer did not enter into the mesoporous channels of MSS. 3.4. pH-Sensitivity of PMV. In order to further examine the pH-dependent volume transition of the PMV shell, the critical texture parameters of samples, surface area (SBET) and pore volume (Vp), were investigated and results were collected in Table 1. The as-synthesized MSS without removal of template showed low SBET (42 m2.g-1) and Vp (0.046 cm3.g-1). The values of SBET and Vp of as-synthesized MSS/PMV without removal of template increased to 488 m2 · g-1 and 0.319 cm3 · g-1, respectively. The increased SBET and Vp should come from the contribution of the PMV shell, not from the MSS core because CTAB still existed in the pores. As seen from Figure 5a,b, the shell of MSS/PMV was made up of a loose polymer network where a large amount of voids existed between polymer chains. Therefore, the SBET and Vp of MSS/PMV were much higher than those of MSS with template. Compared with MSS/PMV, MSS/ PMV-H showed obviously decreased SBET (166 m2.g-1) and Vp (0.186 cm3.g-1). This should result from volume shrinkage of the PMV shell under acidic conditions, which is in agreement with the TEM and SEM results shown in Figure 5 and Figure 6. After ion exchange with NH4NO3/C2H5OH, the SBET and Vp of three samples showed the following values: 710 m2 · g-1 and 0.396 cm3 · g-1 for MSS, 1050 m2 · g-1 and 0.633 cm3 · g-1 for MSS/PMV, but only 203 m2 · g-1 and 0.193 cm3 · g-1 for MSS/ PMV-H (see Table 1). Obviously, the template molecules introduced in the synthesis of MSS and MSS/PMV could be effectively removed, but this ion exchange had less effect on the sample MSS/PMV-H. For MSS, the removal of CTAB was an expectable result in good agreement with the literature.25 For MSS/PMV, the result of ion-exchange was very satisfactory, indicating the polymer shell had good permeability for CTAB transportation. The polymer shell was negatively charged in the process of ion exchange, because PMV had a lower pKa (5-6)

Figure 10. Cumulative release of IBU from MSS/PMV at pH 7.5, pH 5.0, and pH 4.0.

Figure 11. Cumulative release of IBU from MSS at pH 7.5, pH 5.0, and pH 4.0.

than that (∼9.2) of NH4+.25 As a result, the polymer shell was in the “open” state, and allowed CTAB to diffuse through the polymer network. On the contrary, the polymer shell of MSS/ PMV-H kept electrically neutral in NH4NO3/C2H5OH solution, and thus had a compact structure as shown in Figure 5c,d. Therefore, the difficult removal of CTAB from MSS/PMV-H was reasonable if taking into account the MSS pores blocked by compact PMV. 3.5. Drug Loading. The drug-storage test showed that the loading amounts of IBU on MSS and MSS/PMV were 17.4 wt % and 20.3 wt %, respectively (see Table 1), which proved again the good permeability of the PMV shell. At the same time, it was well-known that the -COOH group was more acidic than the ≡Si-OH group. Therefore, during the drug adsorption process, acidic IBU molecules should be adsorbed on the MSS core (containing ≡Si-OH groups) much more than on the PMV shell (containing -COOH groups). Conversely, PMV should indeed adsorb a certain amount of IBU, otherwise, MSS/PMV would not show a higher adsorption amount than MSS. 3.6. In Vitro Drug Release. Figure 10 and Figure 11 show the cumulative IBU release from MSS/PMV and MSS in different release fluids with different pH values (pH ) 4.0, 5.0,

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and 7.5). These pH values were selected based on the fact that PMV had a pKa of 5-6, a range in which it would undergo an abrupt ionization/deionization and thus expansion/shrinkage transition.26 For MSS/PMV, it could be found that IBU release was very fast in the release fluid of pH 7.5, and the release amount reached about 85% within 1 h and almost 100% within 2 h (see Figure 10). This release profile was nearly the same as that of MSS at pH 7.5 (see Figure 11). Therefore, it could be concluded that the polymer shell was in an “open” state at pH 7.5, and did not hinder the transportation of IBU. But in the case of pH 5.0 or 4.0, the release of IBU from MSS/PMV slowed evidently (see Figure 10), and both release amounts were not more than 15% in 8 h. Comparatively, IBU release from MSS could reach 72% and 51% in pH 5.0 and pH 4.0 within 8 h, respectively (see Figure 11), and this relatively slow release was caused by relatively low solubility of IBU in acidic solution. These results indicated that IBU had been effectively confined inside MSS/PMV at low pH. On the whole, the polymer shell had played the role of pore switch in the release of IBU from MSS/PMV by a pH-dependent “open-closed” mechanism. From previous analysis it is known that most IBU molecules exist in the MSS core, and a small amount exists in the polymer shell. Although the polymer shell was compact at low pH, those IBU molecules in the polymer shell also could leach out based on a diffusion-controlled release mechanism similar to pure polymer-based systems.27 So in the cases of pH 5.0 and 4.0, the release amounts of IBU from MSS/PMV still reached about 15% (see Figure 10). However, it was significant that the release amount did not increase after 8 h. This phenomenon indicated that the polymer shell greatly restricted the leaching out of IBU molecules from pores of the MSS core under such a release condition with pH less than 5.0. For targeting drug delivery, it was most desirable that a drug-carrier could show “zero release” before reaching target site, and triggered release upon arriving at the site.1 By so doing, such delivery systems can offer maximum drug efficacy, and reduce toxicity as much as possible. As shown by our findings, the carrier system MSS/PMV was a good candidate for this aim. Through a pH-dependent expand/ compact transition mechanism of the polymer shell, MSS/PMV could carry drugs to pass through low-pH area with “zero release”, and make drugs rapidly release at a targeting site of high-pH. 4. Conclusion In summary, a novel method was proposed to coat PMV on MSS to obtain the core-shell pH-responsive drug-carrier MSS/ PMV. PMV is a pH-responsive polymer because of the presence of ionizable carboxyl groups in its polymeric backbone. At low pH (pKa), ionized PMV polymer chains electrically repulsed and made their volume swell. On this basis, PMV played the role of a molecule switch that controlled the release of drug molecules. Acknowledgment. The financial support from the National Native Science Foundation (No. 20573128) is acknowledged. References and Notes (1) Trewyn, B. G.; Slowing, I. I.; Giri, S.; Chen, H. T.; Lin, V. S. Y. Acc. Chem. Res. 2007, 40, 846. (2) Vallet-Regi, M.; Ra´mila, A.; del Real, R. P.; Pe´rez-Pariente, J. Chem. Mater. 2001, 13, 308. (3) Trewyn, B. G.; Giri, S.; Slowing, I. I.; Lin, V. S. Y. Chem. Commun. 2007, 3236. (4) Vallet-Regi, M.; Ruiz-Gonza´lez, L.; Izquierdo-Barba, I.; Gonza´lezCallbet, J. M. J. Mater. Chem. 2006, 16, 26. (5) Slowing, I. I.; Trewyn, B.; Giri, S.; Lin, V. S. Y. AdV. Funct. Mater. 2007, 17, 1225. (6) Vallet-Regi, M. Chem.sEur. J. 2006, 12, 5934. (7) Horcajada, P.; Ra´mila, A.; Pe´rez-Pariente, J.; Vallet-Regi, M. Microporous Mesoporous Mater. 2004, 68, 105. (8) Andersson, J.; Rosenholm, J.; Areva, S.; Linde´n, M. Chem. Mater. 2004, 16, 4160. (9) Qu, F. Y.; Zhu, G. S.; Huang, S. Y.; Li, S. G.; Sun, J. Y.; Zhang, D. L.; Qiu, S. L. Microporous Mesoporous Mater. 2006, 92, 1. ´ .; Doadrio, A. L.; Pe´rez-Pariente, (10) Izquierdo-Barba, I.; Martinez, A J.; Vallet-Regi, M. Eur. J. Pharm. Sci. 2005, 26, 365. (11) Mun˜oz, B.; Ra´mila, A.; Pe´rez-Pariente, J.; Dı´az, I.; Vallet-Regi, M. Chem. Mater. 2003, 15, 500. (12) Tang, Q. L.; Xu, Y.; Wu, D.; Sun, Y. H.; Wang, J. Q.; Xu, J.; Deng, F. J. Controlled Release 2006, 114, 41. (13) Radu, D. R.; Lai, C. Y.; Wiench, J. W.; Pruski, M; Lin, V. S. Y. J. Am. Chem. Soc. 2004, 126, 1640. (14) Radu, D. R.; Lai, C. Y.; Jeftinija, K.; Rowe, E. W.; Jeftinija, S.; Lin, V. S. Y. J. Am. Chem. Soc. 2004, 126, 13126. (15) Donath, E.; Sukhoruko, G. B.; Caruso, F.; Davis, S. A.; Mo¨hwald, H. Angew. Chem., Int. Ed. Engl. 1998, 110, 2324. (16) Wang, Y. J.; Yu, A. M.; Caruso, F. Angew. Chem., Int. Ed. 2005, 44, 2888. (17) Yu, A. M.; Wang, Y. J.; Barlow, E.; Caruso, F. AdV. Mater. 2005, 17, 1737. (18) Zhu, Y. F.; Shi, J. L.; Shen, W. H.; Dong, X. P.; Feng, J. W.; Ruan, M. L.; Li, Y. S. Angew. Chem., Int. Ed. 2005, 44, 5083. (19) Fu, Q.; Rama-Rao, G. V.; Ista, L. K.; Wu, Y.; Andrzejewski, B. P.; Sklar, L. A.; Ward, S. T.; Lo´pez, G. P. AdV. Mater. 2003, 15, 1262. (20) Hong, C. Y.; Li, X.; Pan, C. Y. J. Phys. Chem. C 2008, 112, 15320. (21) Zhu, Y. F.; Shi, J. L. Microporous Mesoporous Mater. 2007, 103, 243. (22) Nakamura, T.; Mizutani, M.; Nozaki, H.; Suzuki, N.; Yano, K. J. Phys. Chem. C 2007, 111, 1093. (23) Stuart, B. Infrared Spectroscopy: Fundamentals and Applications; Wiley: Chichester, U.K., 2004; Chapter 4. (24) Liu, S. Q.; Lu, L. C.; Yang, Z. X.; Cool, P. G.; Vansant, E. F. Mater. Chem. Phys. 2006, 97, 203. (25) Lang, N.; Tuel, A. Chem. Mater. 2004, 16, 1961. (26) Gil, E. S.; Hudson, S. M. Prog. Polym. Sci. 2004, 29, 1173. (27) Uhrich, K. E. Chem. ReV. 1999, 99, 3181.

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